DNA can be specifically cleaved at nucleotide residues that contain uracil by treatment with uracil DNA glycosylase (UDG) and an AP-lyase. The UDG catalyzes the excision of a uracil base, forming an abasic (apyrimidinic) site while leaving the phosphodiester backbone intact. The AP-lyase breaks the phosphodiester backbone at the 3′ and 5′ sides of the abasic site to release a base-free deoxyribose. This reaction has conventionally been done using the UDG and Endonuclease VIII (Endo VIII) enzymes from E. coli. 
Cleavage of uracil has been exploited to cleave adaptors in preparing samples for sequencing. This workflow typically involves ligating adaptors that contain uracil residues onto nucleic acid fragments, cleaving the adaptors using UDG and AP-lyase (typically in a single reaction using a mix of enzymes), amplifying the fragments using primers that hybridize to the adaptors, and then sequencing the fragments. In some next generation sequencing applications, nucleotides in the fragments are covalently modified after cleavage of the adaptors.
Epigenetic genome markers can be sequenced using for example, bisulfite sequencing. The fragments are deaminated cytosines (C) (but not methylcytosines) are converted to uracil (U). The sequences of the deaminated fragments (or their amplification products) can be analyzed to identify the positions of cytosines and methylcytosines in the original fragments. Unfortunately, conventional uracil-specific cleavage reagents (e.g., E. coli UDG and Endo VIII) can cause non-specific degradation during extended incubation times, or even under conditions that should have inactivated those reagents.